Negative interaction of fatty liver and hypertension on cardiovascular mortality in non-diabetic men: 34 years of follow-up

Figures & data

Table 1. Baseline characteristics and follow-up differences by fatty liver index (FLI) and hypertension (HTN).

		Normal fatty liver index		Borderline fatty liver index		Fatty liver disease
	Total	No HTN	HTN	No HTN	HTN	No HTN	HTN	p Value*
n (%)	1569 (100)	618 (39.39)	94 (5.99)	371 (23.65)	114 (7.27)	238 (15.17)	134 (8.54)
Deaths (column %)	933 (59.46)	304 (49.19)	70 (74.47)	220 (59.30)	85 (74.56)	159 (66.81)	95 (70.90)	<.001
CV deaths (column %)	412 (26.26)	118 (19.09)	42 (44.68)	86 (23.18)	48 (42.11)	69 (28.99)	49 (36.57)	<.001
Non-CV deaths (column %)	521 (33.21)	186 (30.10)	28 (29.79)	134 (36.12)	37 (32.46)	90 (37.82)	46 (34.33)	.221
Age in years	54.42 [48.42, 54.83]	54.33 [48.25, 54.58]	54.42 [54.10, 54.92]	54.42 [48.54, 55.00]	54.50 [54.25, 54.83]	54.33 [48.25, 54.56]	54.42 [50.33, 54.92]	<.001
BMI (column %)								<.001
≤25	511 (32.57)	400 (64.72)	44 (46.81)	47 (12.67)	14 (12.28)	5 (2.10)	1 (0.75)
(25, 27.5]	496 (31.61)	191 (30.91)	44 (46.81)	166 (44.74)	52 (45.61)	34 (14.29)	9 (6.72)
(27.5, 30]	310 (19.76)	27 (4.37)	6 (6.38)	122 (32.88)	41 (35.96)	75 (31.51)	39 (29.10)
(30, 32.5]	163 (10.39)	0 (0.00)	0 (0.00)	33 (8.89)	7 (6.14)	79 (33.19)	44 (32.84)
>32.5	89 (5.67)	0 (0.00)	0 (0.00)	3 (0.81)	0 (0.00)	45 (18.91)	41 (30.60)
Smoking status (column %)								<.001
Never smoker	463 (29.51)	209 (33.82)	31 (32.98)	100 (26.95)	33 (28.95)	56 (23.53)	34 (25.37)
Previous smoker	558 (35.56)	172 (27.83)	32 (34.04)	137 (36.93)	47 (41.23)	103 (43.28)	67 (50.00)
Current smoker	548 (34.93)	237 (38.35)	31 (32.98)	134 (36.12)	34 (29.82)	79 (33.19)	33 (24.63)
Alcohol consumption in g/week	44.00 [12.48, 106.00]	34.85 [10.88, 85.96]	23.31 [6.85, 74.99]	51.00 [21.42, 115.17]	34.83 [7.35, 87.92]	66.25 [22.14, 168.11]	85.45 [20.44, 225.00]	<.001
FLI	33.86 [17.30, 57.42]	15.27 [9.46, 22.33]	20.17 [16.19, 26.05]	42.56 [35.66, 49.38]	43.51 [38.73, 50.77]	74.25 [65.72, 83.49]	79.44 [69.83, 89.52]	<.001
Follow-up in years	28.78 [19.90, 31.13]	29.74 [22.25, 31.67]	24.93 [13.69, 30.69]	28.79 [20.18, 30.87]	26.20 [20.07, 29.87]	26.13 [18.67, 30.58]	24.97 [15.64, 29.92]	<.001
Age of death in years	78.73 [72.59, 84.60]	79.30 [73.00, 85.12]	78.90 [70.41, 84.54]	79.09 [72.76, 84.79]	79.07 [71.94, 84.31]	76.31 [70.69, 80.97]	78.73 [71.05, 84.01]	.002

BMI: body mass index (kg/m²); CV: cardiovascular; eGFR: estimated glomerular filtration rate; HTN: hypertension; RHF: renal hyperfiltration.

Numbers indicate median [interquartile range] unless otherwise indicated.

* The Kruskal–Wallis rank-sum test and the Chi-square test were used for across-groups comparisons.

Table 2. Hazard ratios (HRs) of FLD and hypertension for mortality and cardiovascular outcomes in the study population (n = 1569).

	All-cause mortality			Cardiovascular mortality
	Number of events (n)	Crude HR (95% CI)	Fully adjusted HR (95% CI)	Number of events (n)	Crude HR (95% CI)	Fully adjusted HR (95% CI)
Normal FLI, no hypertension (ref.)	304 (618)	1	1	118 (618)	1	1
Normal FLI, hypertension	70 (94)	1.64 (1.27, 2.13)	1.92 (1.48, 2.50)	42 (94)	2.5 (1.76, 3.56)	2.93 (2.04, 4.19)
Borderline FLI, no hypertension	220 (371)	1.21 (1.02, 1.44)	1.30 (1.06, 1.60)	86 (371)	1.21 (0.91, 1.59)	1.21 (0.87, 1.67)
Borderline FLI, hypertension	85 (114)	1.61 (1.26, 2.04)	1.84 (1.41, 2.40)	48 (114)	2.31 (1.65, 3.24)	2.44 (1.67, 3.56)
FLD, no hypertension	159 (238)	1.73 (1.42, 2.09)	1.79 (1.37, 2.34)	69 (238)	1.93 (1.44, 2.6)	1.70 (1.12, 2.58)
FLD, hypertension	95 (134)	1.67 (1.33, 2.11)	1.74 (1.27, 2.39)	49 (134)	2.18 (1.56, 3.05)	1.89 (1.18, 3.01)
	Non-cardiovascular mortality
Normal FLI, no hypertension (ref.)	186 (618)	1	1
Normal FLI, hypertension	28 (94)	1.09 (0.73, 1.62)	1.27 (0.85, 1.90)
Borderline FLI, no hypertension	134 (371)	1.22 (0.97, 1.52)	1.38 (1.05, 1.81)
Borderline FLI, hypertension	37 (114)	1.15 (0.81, 1.64)	1.41 (0.96, 2.07)
FLD, no hypertension	90 (238)	1.6 (1.24, 2.05)	1.87 (1.31, 2.66)
FLD, hypertension	46 (134)	1.34 (0.97, 1.85)	1.63 (1.06, 2.50)

CI: confidence interval; FLD: fatty liver disease; FLI: fatty liver index score; ref.: reference category.

Crude HRs are hazard ratios adjusted for age only. Fully adjusted HRs were adjusted for age, body mass index, smoking, the interaction between body mass index and smoking, and alcohol consumption.

Figure 1. Fully adjusted hazard ratios (HRs) with 95% CIs for all-cause mortality, cardiovascular mortality and non-cardiovascular mortality stratified by fatty liver index and hypertension categories. FLD: fatty liver disease; FLI: fatty liver index.

Table 3. Estimates of the biological interaction of fatty liver disease and hypertension on mortality and cardiovascular outcomes.

Outcome	Multiplicative scale^a	RERI^b	Synergy index^b
Age-adjusted Cox proportional hazard models
All-cause mortality	0.59 (0.41, 0.85)**	–0.65 (–1.32, 0.01)	0.58 (0.34, 0.99)*
CV mortality	0.45 (0.27, 0.75)**	–1.27 (–2.54, 0.01)	0.54 (0.3, 0.97)*
Non-CV mortality	0.77 (0.45, 1.32)	–0.26 (–0.99, 0.47)	0.66 (0.21, 2.05)
Fully adjusted Cox proportional hazard models
All-cause mortality	0.51 (0.35, 0.74)***	–0.97 (–1.65, −0.28)**	0.44 (0.23, 0.83)*
CV mortality	0.38 (0.23, 0.64)***	–1.74 (–2.98, −0.5)**	0.34 (0.14, 0.8)*
Non-CV mortality	0.68 (0.4, 1.17)	–0.52 (–1.33, 0.3)	0.55 (0.2, 1.47)

CI: confidence interval; CV: cardiovascular; RERI: relative excess risk due to interaction.

* Significant at p<.05.

** Significant at p<.01.

*** Significant at p<.001.

^a Hazard ratio of the multiplicative interaction between fatty liver disease and hypertension estimated from the interaction models. Estimates lower than 1 suggest antagonism.

^b Estimated from the hazard ratios of the models including the composite variable of fatty liver disease and hypertension departing from an additive scale. RERI lower than 0 or synergy index lower than 1 suggests antagonism.

Figure 2. Fully adjusted survival curves for all-cause mortality, cardiovascular mortality and non-cardiovascular mortality. FLI: fatty liver index.

Data availability statement

The University of Eastern Finland can be approached for requests of access to the KIHD dataset.